The invention relates to compositions and methods for treatment of cold sores or fever blisters, and canker sores, herpes labialis and aphthous stomatitis lesions.
There are a number of over-the-counter medications for cold sores, fever blisters and the like, including BLISTEX, ZILACTIN, and CAMPHO PHENIQUE. A prescription medication also is available, under the trademark ZOVIRAX. However, for many persons suffering from cold sores, fever blisters, etc., none of these medications is very effective.
Histamine phosphate previously has been used as a diagnostic agent for determining how much acid the human stomach produces. Histamine phosphate also has been used for injection in human skin to cause a flare-up reaction indicative of the ability of certain drugs to inhibit histamine-induced wheals, thereby indicating clinical response in allergenic diseases.
The histamine phosphate referred to is the compound 1H-imidazole-4-ethanamine phosphate (IEP), and is currently used in subcutaneous injection for the diagnosis of gastric function. Principal effects of IEP from subcutaneous, intramuscular or intravenous administration occur on the vascular system, smooth muscles, and exocrine glands. In humans, IEP produces vasodilation in the small blood vessels and capillaries causing a flushing of the face, reduction in systemic blood pressure, increase in skin temperature, and increased capillary permeability sufficient to produce exudation of fluid, plasma proteins, and erythrocytes into extracellular spaces.
Intracutaneous injection of 0.01-0.02 milligrams of IEP can create a characteristic "triple response" including a reddening at the site of the injection, a wheal or patch of localized edema within 20-60 seconds, followed by a bright halo or a flare around the wheal.
There is considerable species variation with regard to the response of smooth muscles to IEP. In humans, IEP stimulates smooth muscle contraction of the gastro-intestinal (GI) tract, contraction of the sphincter of Oddi and bile duct, and potent bronchoconstriction in patients with bronchial asthma, emphysema, or bronchitis. IEP has little effect on the smooth muscle of the uterus and has little bronchoconstrictor effect on healthy individuals.
IEP is metabolized in the liver by methylation and oxidation, and the metabolites are excreted in the urine. IEP is largely inactive when given by mouth. No information has been found regarding the extent of systemic absorption following topical administration of IEP. It has been suggested by Kahlson et al. that exogenous IEP might play a beneficial role in the healing process of certain types of tissue damage. The CARBOPOL gel base is widely used in the cosmetic industry and has been proven safe.
Recurrent herpes simplex stomatitis may occur on the lips or intraorally. Outbreaks may be associated with trauma, fatigue, menstrual cycle, emotional upset, or exposure to sunlight. Vesicles, or intraepithelial blisters, usually are preceded by burning, swelling and soreness in the area where lesions subsequently develop. Vesicles are small, 1 millimeter in diameter or less, and may coalesce to form larger lesions. These vesicles rupture quickly, leaving small ulcerations. The most common sites of recurrent intraora lesions are the hard palate and attached gingiva. Lesions gradually heal within 7-10 days producing no scarring.
Canker sore lesions are characterized by the development of painful, recurring necrotizing ulcerations of the oral mucosa either as solitary or multiple lesions. Etiology is unclear; however, considerable evidence suggests the disease may be an immunologic hypersensitivity response to an L-form streptococcus bacterium. Precipitating factors in canker sore lesions may include trauma (dental procedures), self-inflicted bites (as in eating), endocrine changes (premenstrual periods, following childbirth, menopause), acute psychological problems (period of increased stress), and allergic responses (asthma, eating certain foods or taking certain medications).
The aphthous ulcer can begin as a single or a multiple superficial erosion covered by a gray membrane. The most common sites of occurrence are the mucosa of the lips and cheeks, soft palate, tongue, pharynx, and all locations of unattached (to bone) gingiva and mucosa. The ulcers persist for 7 to 10 days and heal gradually producing no scarring.
There is an unmet need for an effective remedy for fever blisters, cold sores, canker sores, gum ulcers, etc.